Project Summary Prior to implementing universal childhood vaccination in Alaska, rates of hepatitis A in Alaska Native persons were more than five times higher than those in other racial/ethnic populations.[2] Further data are needed to determine the possible requirement of hepatitis A vaccine booster doses to ensure continued protection. Hepatitis B virus (HBV) can cause chronic infection, resulting in cirrhosis of the liver, liver cancer, liver failure, and death.[4] [5] Much like the hepatitis A vaccine, hepatitis B immunization strategies for infants, children, adolescents and adults have significantly decreased the incidence and prevalence of acute and chronic hepatitis B infection.[6] The complete duration of protection after primary vaccination with hepatitis B vaccine and thus whether booster doses of vaccine to maintain protection against HBV infection are required is undetermined. There is elevated importance for persons who initiated hepatitis B vaccination at birth. Recent data, including that from the Alaska Native Tribal Health Consortium, Liver Disease and Hepatitis Program research team, suggest an increased proportion of persons vaccinated as newborns lose protective antibody compared with those vaccinated as children or adults.[7, 8] Prior to hepatitis B vaccination, prevalence of hepatitis B infection amongst Alaska Native persons was endemic.[9] Although hepatitis B incidence has declined dramatically since implementation of vaccination among Alaska Native infants, children and adults, there remain a substantial number of Alaska Native persons chronically infected with HBV and remain at an increased risk of disease sequelae including hepatocellular carcinoma.[10] Alaska Native persons chronically infected with HBV also exhibited increased incidence of hepatocellular carcinoma amongst younger people.[11] In addition to chronic HBV, other chronic liver disease etiologies including chronic hepatitis C, non- alcoholic fatty liver disease and autoimmune hepatitis have been shown to cause substantial morbidity and mortality among Alaska Native persons.[12] [13] Further complication in the clinical management of chronic hepatitis B and C in Alaska is due to the remoteness of the population and the lack of access to specialty care. New diagnostic tests are needed that are less invasive, more sensitive and do not require specialty clinical service. We propose to address these public health issues by determining the further duration of vaccine protection afforded by both hepatitis A and hepatitis B vaccines in children and adults in well-established longitudinal cohorts. We also intend to measure the effectiveness and impact of clinical interventions on mortality and morbidity associated with chronic hepatitis B and chronic hepatitis C including screening, early diagnostics and treatment. To safely delay the need for booster doses of either hepatitis A or hepatitis B vaccines can result in both safety from exposure to these viruses and healthcare cost savings. Understanding the influence of clinical interventions can provide new diagnostic tools for chronic viral hepatitis outcome as well as new clinical management strategies that could be useful to apply in a variety of healthcare settings.